One of biology’s key challenges is understanding how the complexity of life arises from just four nucleotide "letters" in the genetic code. Thus, this project aims to explore the mechanisms behind gene expression, the process by which this genetic information is brought to life. In the initial step of gene expression, the DNA is copied into messenger RNA (mRNA). Among other things, this mRNA is then packaged by proteins into a complex known as an mRNP (messenger ribonucleoprotein particle) and exported from the cell’s nucleus to its cytoplasm, where it directs protein synthesis. The assembly of mRNPs is not only essential for gene expression but also for the regulation this process. Disruptions in mRNP assembly are linked to a variety of diseases like neurological disorders (e. g. ALS), cancer and viral infections, such as HIV or influenza, highlighting its importance. Consequently, mRNP assembly is particularly important under stress, including illness or viral infection.
By deciphering the molecular mechanisms of mRNP assembly and how they change under stress, this project advances our understanding of gene regulation and provides a foundation for developing new therapies targeting mRNP-related diseases, offering significant societal and public health benefits.
During this project, we established the biochemical purification of a specific nuclear mRNP, i.e. a nuclear mRNP containing one specific mRNA, and initiated its structural analysis. We published the structure of the central complex TREX (doi: 10.1261/rna.079758.123) solved the structure of an mRNP component and analysed a trimeric mRNP subcomplex (to be published). Importantly, we revealed the functions of the mRNP component Npl3 (doi: 10.1093/nar/gkac1206) and of the Prp19C components Syf2 and Cwc15 (doi: 10.1261/rna.079944.124). In addition, we unravelled the function of three more mRNP components (to be published in three manuscripts) and analysed changes in mRNP assembly under stress (to be published). The importance of this project is also reflected by three review articles (dois: 10.1007/978-3-030-31434-7_1 10.1002/wrna.1582 10.3390/biom10091310) and one accepted review about mRNP assembly under stress (accepted in the Journal Molecular Cell, currently under embargo).
The overarching objective is to unravel mRNP assembly mechanisms and stress-related changes, providing the knowledge for future therapeutic developments.
